Elsevier

Biochemical Pharmacology

Volume 42, Issue 8, 27 September 1991, Pages 1529-1535
Biochemical Pharmacology

The role of specific cytochromes P450 in the formation of 7,12-dimethylbenz(a)anthracene-protein adducts in rat liver microsomes in vitro

https://doi.org/10.1016/0006-2952(91)90421-ZGet rights and content

Abstract

The role of specific cytochrome P450 (P450) isoforms in the formation of adducts of 7,12-dimethylbenz (a)anthracene metabolites and membrane proteins has been investigated in vitro with microsomal fractions prepared from rats pretreated with various isoenzyme selective inducers. The effects of isoenzyme selective inhibitors were also evaluated. Adduct formation was shown to be mediated by P450 catalysed reactions but was unaltered, relative to untreated animals, in membranes from pyrazole- and clofibrate-treated animals suggesting that CY P2E1 and CYP4A1 are not involved in this process. However, adduct formation was significantly increased in microsomes from Sudan III-,phenobarbital-and dexamethasone-treated rats, suggesting the involvement of the CYP1A, CYP2B and CYP3A subfamilies, respectively. These conclusions were further supported by the finding that adduct formation in these microsomes could be inhibited by the isoenzyme-selective inhibitors α-naph-thoflavone, metyrapone and troleandomycin, respectively.

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